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Spontaneous tumour regression in keratoacanthomas is driven by Wnt/retinoic acid signalling cross-talk

Author

Listed:
  • Giovanni Zito

    (Yale Stem Cell Center, Yale Cancer Center, Yale School of Medicine)

  • Ichiko Saotome

    (Yale Stem Cell Center, Yale Cancer Center, Yale School of Medicine)

  • Zongzhi Liu

    (Yale Cancer Center, Yale University School of Medicine)

  • Enrico G. Ferro

    (Yale Stem Cell Center, Yale Cancer Center, Yale School of Medicine)

  • Thomas Y. Sun

    (Yale Stem Cell Center, Yale Cancer Center, Yale School of Medicine)

  • Don X. Nguyen

    (Yale Cancer Center, Yale University School of Medicine)

  • Kaya Bilguvar

    (Yale Stem Cell Center, Yale Cancer Center, Yale School of Medicine)

  • Christine J. Ko

    (Yale School of Medicine)

  • Valentina Greco

    (Yale Stem Cell Center, Yale Cancer Center, Yale School of Medicine
    Yale School of Medicine)

Abstract

A fundamental goal in cancer biology is to identify the cells and signalling pathways that are keys to induce tumour regression. Here we use a spontaneously self-regressing tumour, cutaneous keratoacanthoma (KAs), to identify physiological mechanisms that drive tumour regression. By using a mouse model system that recapitulates the behaviour of human KAs, we show that self-regressing tumours shift their balance to a differentiation programme during regression. Furthermore, we demonstrate that developmental programs utilized for skin hair follicle regeneration, such as Wnt, are hijacked to sustain tumour growth and that the retinoic acid (RA) signalling pathway promotes tumour regression by inhibiting Wnt signalling. Finally, we find that RA signalling can induce regression of malignant tumours that do not normally spontaneously regress, such as squamous cell carcinomas. These findings provide new insights into the physiological mechanisms of tumour regression and suggest therapeutic strategies to induce tumour regression.

Suggested Citation

  • Giovanni Zito & Ichiko Saotome & Zongzhi Liu & Enrico G. Ferro & Thomas Y. Sun & Don X. Nguyen & Kaya Bilguvar & Christine J. Ko & Valentina Greco, 2014. "Spontaneous tumour regression in keratoacanthomas is driven by Wnt/retinoic acid signalling cross-talk," Nature Communications, Nature, vol. 5(1), pages 1-13, May.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4543
    DOI: 10.1038/ncomms4543
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